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The structure of apixaban, before adjusting the moiety's for maximum potency. Apixaban. The 13F moiety intermediate before apixaban was fully developed. During the SAR development of apixaban there were three groups that needed to be tested to attain maximum potency and bioavailability.
Direct factor Xa inhibitors include rivaroxaban, apixaban and edoxaban, and are types of direct oral anticoagulant (DOAC), which are blood thinning drugs, one of the classes of antithrombotic drugs.
No approved antidotes for edoxaban overdose exist as of April 2021. [4] Hemodialysis does not significantly contribute to edoxaban clearance. [3] [12] Andexanet alfa has been studied as an antidote for edoxaban overdose, but has only been approved for reversing rivaroxaban and apixaban effects by the FDA and the EMA as of 2019. [13] [14]
Apixaban is a highly selective, orally bioavailable, and reversible direct inhibitor of free and clot-bound factor Xa. Factor Xa catalyzes the conversion of prothrombin to thrombin, the final enzyme in the coagulation cascade that is responsible for fibrin clot formation. [ 27 ]
Based on limited evidence, the consensus appears to be that in most patients who are receiving the newer direct-acting oral anticoagulants (i.e., dabigatran, rivaroxaban, apixaban, or edoxaban) and undergoing dental treatment (in conjunction with usual local measures to control bleeding), no change to the anticoagulant regimen is required.
Rivaroxaban, Apixaban and Edoxaban bind to the active site of factor Xa, regardless of whether factor Xa is bound in the prothrombinase complex or is in its free form. [ 35 ] [ 37 ] These direct factor Xa inhibitors can be administered orally, as can dabigatran etexilate , which is a direct thrombin inhibitor.
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Clinical approaches on how to overcome clopidogrel resistance include higher doses of clopidogrel, concomitant use with the phosphodiesterase inhibitor cilostazol or switching to a new antiplatelet agent such as prasugrel and ticagrelor. Still, the major concern with these methods above are increased risk of bleeding.